High Canal Institute of Engineering & Technology, Suez, Egypt.
Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Giza, Egypt.
Sci Rep. 2024 Apr 20;14(1):9106. doi: 10.1038/s41598-024-59072-w.
Coumarins are heterocycles of great interest in the development of valuable active structures in chemistry and biological domains. The ability of coumarins to inhibit biofilm formation of Gram positive bacterium (Staphylococcus aureus), Gram negative bacterium (Escherichia coli) as well as the methicillin-resistant S. aureus (MRSA) has been previously described. In the present work, new hybrid coumarin-heterocycles have been synthesized via the reaction of coumarin-6-sulfonyl chloride and 6-aminocoumarin with different small heterocycle moieties. The biological efficacy of the new compounds was evaluated towards their ability to inhibit biofilm formation and their anti-inflammatory properties. The antimicrobial activities of the newly synthesized compounds were tested against Gram positive bacterium (S. aureus ATCC 6538), Gram negative bacterium (E. coli ATCC 25922), yeast (Candida albicans ATCC 10231) and the fungus (Aspergillus niger NRRL-A326). Compounds 4d, 4e, 4f, 6a and 9 showed significant MIC and MBC values against S. aureus, E. coli, C. albicans, and methicillin-resistant S. aureus (MRSA) with especial incidence on compound 9 which surpasses all the other compounds giving MIC and MBC values of (4.88 and 9.76 µg/mL for S. aureus), (78.13 and 312.5 µg/mL for E. coli), (9.77 and 78.13 µg/mL for C. albicans), and (39.06 and 76.7 µg/mL for MRSA), respectively. With reference to the antibiofilm activity, compound 9 exhibited potent antibiofilm activity with IC of 60, 133.32, and 19.67 µg/mL against S. aureus, E. coli, and MRSA, (respectively) considering the reference drug (neomycin). Out of all studied compounds, the anti-inflammatory results indicated that compound 4d effectively inhibited nitric oxide production in lipopolysaccharide-(LPS-) stimulated RAW264.7 macrophage cells, giving NO% inhibition of 70% compared to Sulindac (55.2%).
香豆素是化学和生物领域中具有重要价值的活性结构开发的杂环化合物。先前已经描述了香豆素抑制革兰氏阳性菌（金黄色葡萄球菌）、革兰氏阴性菌（大肠杆菌）以及耐甲氧西林金黄色葡萄球菌（MRSA）生物膜形成的能力。在本工作中，通过 6-磺酰基香豆素与 6-氨基香豆素与不同的小杂环部分的反应合成了新的香豆素-杂环化合物。通过它们抑制生物膜形成的能力和抗炎特性评估了新化合物的生物学功效。新合成化合物的抗菌活性针对革兰氏阳性菌（金黄色葡萄球菌 ATCC 6538）、革兰氏阴性菌（大肠杆菌 ATCC 25922）、酵母（白色念珠菌 ATCC 10231）和真菌（黑曲霉 NRRL-A326）进行了测试。化合物 4d、4e、4f、6a 和 9 对金黄色葡萄球菌、大肠杆菌、白色念珠菌和耐甲氧西林金黄色葡萄球菌（MRSA）具有显著的 MIC 和 MBC 值，特别是化合物 9 表现出优于所有其他化合物的活性，其 MIC 和 MBC 值分别为（金黄色葡萄球菌 4.88 和 9.76μg/mL）、（大肠杆菌 78.13 和 312.5μg/mL）、（白色念珠菌 9.77 和 78.13μg/mL）和（MRSA 39.06 和 76.7μg/mL）。在抗生物膜活性方面，化合物 9 对金黄色葡萄球菌、大肠杆菌和 MRSA 的 IC 分别为 60、133.32 和 19.67μg/mL，表现出很强的抗生物膜活性（与参考药物新霉素相比）。在所研究的化合物中，抗炎结果表明化合物 4d 有效抑制脂多糖（LPS）刺激的 RAW264.7 巨噬细胞中一氧化氮的产生，与舒林酸（55.2%）相比，NO%抑制率为 70%。
